Preparation of secondary aryl- and aralkylamines



Patented Oct. 18, 1932 UNITED STATES PArsNn OFFICE EDGAR C. BRITTON AND HAROLD R. SLAGH, OF MIDLAND, MICHIGAN, ASSIGNORS TO THE DOW CHEIJIICAL COMPANY, OF MIDLAND, MICHIGAN, A CORPORATION OF MICHIGAN PREPARA'IION OF SECONDARY ARYL- AND ARALKYLAMINES No Drawing.

ary arylamines is described in British Patent 250,819, wherein nuclear substitution products'of diphenylamine are formed by causing a nuclear halogen substitution product of a benzene hydrocarbon to act on an alkalimetal compound of a primary aromatic amino-body of the benzene serles, if desired, 1nthe presence of a catalyst, either one or both of the reacting substances containing at least one nuclear substituent in addition to the halogen atom or amino-group. The temperature disclosed therein asnecessary for the aforesaid reaction is 250 to 300 C. We have now devised certain useful 1mprovements whereby more advantageous op-( erating conditions are provided, high yields of principal products may be attained and a wider range of compounds of the character in hand may be prepared. To the accomplishment of the foregoing and related ends,

the invention, then, consists of the steps hereinafter fully described and particularly pointed out in the claims, the following description setting forth detail procedures embodying the invention, these being illustrative however of but several of the ways in which the principle of our invention may be used.

The present 1nvent1on involves important 0 distinctions over the aforementioned method, and more particularly in accordance l1erewith (1) The reaction may be caused to proceed at temperatures materially lower than those stated in the aforesaid patent, and indeed,

at a temperature as low as 110 C.:

(2) It is not essential that 'eitherof the reacting substances shall contain a nuclear substituent in addition to the halogen or ami; no-group; for example, diphenylamine itself Application filed January 18, 1929. Serial No. 333,514.

substituted derivatives thereof:

(3) Other metallic derivatives of apri-. mary aromatic amine may be employed'ass well as the alkali-metal derivatives thereof; for example, the corresponding calcium, aluminum or magnesium anilides:

(4:) It is not essential that a halogen substituted benzene or other aromatic hydrocarbon be employed to react upon the metallic anilide, and the reaction takes place equally well with alkyl halides:

(5) The reaction product contains a measurable amount of aryl or alkyl-substituted primary arylamine corresponding to and accompanying the principal secondary amine product; in general the higher the temperature the greater the amount of such primary amine is formed. i A

The present invention, therefore, comprehends a method for the preparation of secondary arylamines or aryl-alkyla-mines and nuclear'substituted derivatives thereof, together. with a greater or lesser amount of the corresponding arylor alkyl-substituted primary amine. The reactions involved may be illustrated by the following equations leading in the formation of diphenylamine and amine-diphenyl, viz a 1 ofinmn naeo n nnnwn aniline slqqig zg chlordiphenylbenzene amine oanao n nn asnaci amino-diphenyl The principal reaction between the metallic anilide and chlorebenzene leading to the fore mation of a secondary amine is represented operation. The simultaneous formation of the two isomeric compounds, diphenylamine and amino-diphenyl, may possibly be due to the existence of tautomeric forms of the metallic anilide, as shown by the formulae, viz:

NHa C aHaNHNa 01 G 0H4 benzene, or substituted derivatives of such halogenated hydrocarbons, as for example, chlor-phenols and ethers thereof, chlor-ca rboxylic or sulphonic acids, etc. lVhen such phenols or acids are employed for the reaction they should be introduced in the form'of their alkali-metal salts.

The relative preponderance of Equation (2) as opposed to Equation (3) is determined largely by the reaction temperature, and to a lesser. extent by the specific metal employed.

to form the metallic anilide as in Equation (1). Suitable reaction temperatures are found in the range between 100 and 250 C or higher. compounds react at somewhat lower temperatures than the corresponding chlor-compounds. With any given combination of reactants and within the range of temperatures at which a substantial conversion is realized, the lower temperatures within such range will favor the reaction as represented by Equation (2), while increasing the temperature tends to promote the reaction represented by Equation 3).

As a rule pressure is not essential for consummating the reaction, but at times may be advantageously employed in case the preferred reaction temperature is above the boil- "ing point of'oneof'the' reactants. In such case, however, a reflux condenser can often be employed with equal advantage, the condensed vapors being continuously returned to the reaction. A solvent for the reaction constituents may be advisedly employed, which may consist of an excess of one of the reactants, orof some additional non-reactive solvent, or of a mixture of same. Another,

function of such solvent at times may be to serve as a temperature modifying liquid for In general, brom-subst-ituted regulating the boiling point of the reaction mixture.

By way of illustration the following detailed examples aregiven, but it is understood that such examples are not to be con sidered as a limitation upon the invention.

Ewample 1.'825 grams dry aniline and 23 grams sodium with a trace of cuprous oxide were heated to a temperature of about 170 to 180 (1, heating being continued for approximately 3 hours or until evolution of hydrogen ceased. The temperature of the mixture was then allowed to fall to about 150 C. and 115 grams chlorbenzene were run in drop by drop during about 1 hour, and the mixture maintained at a temperature of 150 to 160 for 7 hours longer. As the reaction proceeded sodium chloride crystals were precipitated. The reaction mixture was then cooled and treated with waterto dissolve the salt and the oil layer separated from the aqueous salt solution. The oil layer was fractionally distilled under reduced pressure, the products obtained being unreacted chlorbenzene, excess aniline and finally a' mixture of diphenylamine and amino-diphenyl, a small amount of tarry residue remaining in the still. The mixture of diphenylamine and amino-diphenyl was treated with dilute hydrochloric acid, which dissolved amino-diphenyl, leaving diphenylamine as pure white crystals which were filtered from the solu-.

tion. The acid solution was then neutralized with caustic soda solution 'to precipitate amino-diphenyl crystals which were filtered off; The product consisted of 88 grams diphenylamine and 13' grams aminodiphenyl. Titration of the aqueous salt solution for chlorides indicated a 75.2 per cent. conversion based upon the quantity of sodium used, in'accordance with the Equations (1) (2) and (3) above, the balance of the original charge being recovered as unreacted aniline and .chlorbenzene. The yield of product was 59.7 per cent. based upon the raw materials taken, or 7 9 per cent. based upon the chlorbenzene actually reacted and consumed.

In the foregoing example an excess of aniline was employed as solvent for the reaction. Another solvent, as toluene, diphenyl oxide or the like, may be used if desired, but aniline is satisfactory for the purpose and is readily separated and recovered from the reaction product. If brombenzene is used in. the reaction instead of chlorbenzene, the reaction temperature is reduced to about 110 C. In working up the product by treating with hydrochloric acid solution, the primary amine constituent dissolves therein with salt formation, whereas the weakly basic secondary amine does not react with the dilute acid and remains undissolved. This procedure is of general application for separating the products obtained by my improved method.

weaves I autoclave at a temperature of 175 to 180CI for 13 hours.

for 3 hours, the hydrogen formed being released at a pressure of about pounds. 150 grams chlorbenzene was then added and the mixture heated to 200 C. under pressure The reaction product was worked up as in'Examp-le 1. There wereobtained 106 grams diphenylami-ne and 58 grams amino-diphenyl; Chlorine titration showed 90.6 per cent. conversion of chlorbenzene. The yield of product was '7 5 per a cent. of theory, or 81.7 per cent.'*based upon consumption of chlorbenzene. 1

Example 3.Sodium anilide' was formed by heating-130 grams dry aniline, 10 gra ns sodium with a trace of 'cuprous oxide for 3 hours at 17 0 to 180 C. The mixture was transferred toan iron bomb, 55 grams chlorbenzene added, and the whole hea ted under pressure at 250 to 300 C. for 25 minutes. Fromthe product were obtained an grams diphenylamine and 16 grams :amino-dip-henyl.

Conversion of chlorbenzene as shown by chloride titrationwa's 90 per cent; yield of product 76.3 per centfof theory, or 83:6 per cent. of material actually consumed;

'Emample 4.'In similar manner, sodium anilide and para-chlortoluene heated together at 175 to 180 C. for 5ho ursgave 'a' 74.3 per cent. yield of product consisting of 7 5 per cent. phenyl-tolyl' amine and 25 per cent.

amino-methyl-diphenyl. Based upon material actually consumed the total yield was 80 per cent.

E maa'nqole 5. Sodium anilid'e andsa-chlornaphthalene heated together for 5 hours at 170 to 180 C. gave a 64.5 per cent. yield of product consisting of 80 percent. phenyloc-naphthylamine and 20 per cent. aminophenyl-naphthyl. The yield based upon materials actually consumed was 68 per cent.

Example 6.325 grams dry aniline and 9 grams potassium, with a trace of cuprous oxide, were heated at 110 to 115 C. for 1 hour. Then 28 grams chlorbenzene was added and the mixture heated at 170 'to 175 C. for 6 hours. The yield was 56.4 per cent. of a product consisting of 85.6 per cent. diphenylamine and 1 1.4 per cent. amino diphenyl. Based upon materials actually consumed the yield was 83 per cent.

Err/ample 7.-200 grams of dry aniline and 5 grams aluminum, with a trace of cuprous oxide, were heated at 180 C. for 16 hours. Then 63 grams chlorbenzene were added and the mixture heated at 180 C. for 7 hours.

1 The yield was 40 per cent. and conversion of 3 0 cent. amino-diphenyl.

' added, and the mixture heated at 180 C.

for 8 hours. The yield was 51 per cent. and conversion of chlorbenzene 58.5 per cent, correspondingto an 87 per cent. yield based upon materials actually consumed. The product consisted of 78 per cent. diphenylamine and 22 per cent. amino-diphenyl.

Emamp'le .9.-200 grams aniline and 11 grams sodium, with a trace of cuprous oxide, were heated at 180 C. for-3 hours. "68 grams norma'l'butyl bromide were then added, and the mixture heated at 150 C. for 3 hours. The yield was 77 per cent. of a product 'containing 93.1 per cent. n-butyl aniline and 6.9 per cent. .amino-butyl-benzene.

In the foregoing examples various specific applications of the principle of our invention have'been described with reference to derivatives of aniline formed by reaction of a metallic anilide with a mono-halogenated aromatic or aliphatic hydrocarbon, irrespec-v aromatic nucleus of one or other of the re-1 acting substances. It isseen from Examples 1, 2 and 3 that the ratio of secondaryamine to substituted primary amine in the reaction product is. higher at the lower reaction temperatures,; and that as the temperature is increased the proportion of substituted primary amine in the product likewise increases. In Example 3 the production of dip'heny'lamine itself in good yield,together with some amino-diphenyl, is shown under conditions whereby only nuclear substitution products thereof had been previously .found possible of formation. In further examplesv the preparation of derivatives of other halogenated aromatic hydrocarbons than chlore benzene is illustrated as well as similar derivatives of an aliphatic halide, and likewise the procedure for utilizing other metallic ani'lides derived from metals of Groups I, II and III.

It is understood thatsimilar derivatives of primary aromatic amines generally may be prepared in analogous fashion by reacting between the corresponding metallic anili'de or homologous arylamide and a halogenated aromatic or aliphatic, hydrocarbon. Still further, compounds of related constitution may be formed by reacting between a suit.

able metallic arylamide and a poly-halog- .enated aromatic or aliphatic hydrocarbon,

as for example ethylene dichloride, dichlorbenzene, dichlorna-phtha'lene, and the like. By suitable manipulation and properly proportioning the relative quantities of reactants employed either one or more of the halogen at ms of the poly-halogenated 'hy-' drocarbon may bev caused to react. Thus:

be employed. a

stepwise operation is feasible, yielding first halogen substituted amino compounds, and finally a'completely dehalogenated product. If desired the reaction may be controlled to produce said halogen substituted compounds as end products. 7 In preparing the metallic anilide orarylamide the use of a catalyst, such as cuprous oxide, facilitates the reaction, but such use of a catalyst is not essential to the invention.

Other modesof applying the principle of our invention may be employed instead of the one explained, change being made as regards the detail herein disclosed, provided the step or steps stated by any of the following claims or the equivalent of such stated step or steps .In the claimstheterm metallic anilide comprehends broadly any compound of the general formula AryLNI-LMet formed by reacting a primary arylamine with one molecular equivalent of a metal reactive therewith.

-We'therefore particularly point out and distinctly claim as our invention 1. The method of making conj ointly a sec ondary arylamine having the general formula Aryl.NH.R and the corresponding primary arylamine having the general formula RAryLNH wherein R'represents an aryl or alkyl group, which comprises reacting a metallic anilide of a metal from the group consisting of Na, K,-Ca, Mg and A1, with a halogenated hydrocarbonhaving the general formula'RHal, wherein R is aryl or alkyl, at a temperature between 100 and 250 C. p a Y 2; The method of making conjointly a secondary arylamin'e having the general formula Aryl.NI-I.R and thecorresponding primary arylamine having the general formula RAryLNI-L, wherein R represents an aryl or alkyl group, which comprises reacting aniline with not'more than one molecular equivalent of a metal from the group consisting of Na, K, Ca, Mg and Al, to form the corresponding metallic anilide, adding a halogenatedhydrocarbon having the general formula Rl-Ial, wherein R is alkyl -or aryl, and heating at a temperature between 100 and 250 C.

3. The method of making a secondary aralkyl amine and the corresponding nuclear alkyl-substituted primary arylamine which comprises reacting aniline with not more than a one molecular equivalent of a metal from the" group consisting of Na, K, Ca, Mg and Al, to form the corresponding metallic anilide, adding an alkyl halide and heating at a temperature between 100 and 250C;

4. The method of making a diarylamine and the corresponding nuclear arylsubstituted primaryarylamine which comprises reacting aniline with not more than one molecular equivalent of a metal from the group consisting of Na, K, Ca, Mg and Al, to form the corresponding metallic anilide, adding a monohalogenated aromatic hydrocarbon and heatiig at a temperature between 100 and 250 5. The method of making diphenylamine and amino-diph'enyl which comprises reacting aniline with not more than one molecular equivalent of a metal from the group consisting of Na, K, Ca, Mg and Al, to form the corresponding metallic anilide, adding chlorobenzene and heating at a temperature between 100 and 250 C.

6. The method of making diphenylamine and amino-diphenyl which comprises heat-ing aniline with not more than one molecular equivalent of sodium, adding chlorobenzene to the resulting product and heating at a temperature between 100 and 250 C. p 7. In a method of making a diarylamine and the corresponding amino-diaryl, the step which consists in reacting a metallic anilide of the f0rmula'C H .NH.Met wherein Met represents Na, K, Ca, Mg or A1, with a monohalogenated aromatic hydrocarbon at a temperature between 100 and 250 C.

8. In a method of making a diarylamine and the corresponding amino-diaryl, the step which consists in reacting a metallic anilide of the formula G H .NH.Met', wherein Met represents Na, K, Ca,'Mg or A1, with a monohalogenated benzene at a temperature be-- tween 100 and 250 C.

9. In a' method of making diphenylamine and amino-diphenyl conjointly, the step which consists in reacting sodium anilide with chlorobenzene at a temperature between 100 and 250 C.

Y Signed by us this 11 day of January, 1929.

a EDGAR C. BRITTON.

HAROLD R. SLAGH. 

